Oxaliplatin, CAS Number [61825-94-3], is the generally used name for the (SP-4-2)-[(1R,2R)-1,2-cyclohexanediamine-kN,kN′]-[ethanedioato(2-)-kO1,kO2]platinum(II) complex of the structural formula I:

Oxaliplatin was first reported by the Nagoya City University, Japan, in Gann, 1976, 67(6), 921-2. Oxaliplatin is frequently used in cancer therapy. A general method for preparing oxaliplatin is described in prior art, e.g. in U.S. Pat. No. 4,169,846. The process described there is based on the reaction of a solid (SP-4-2)-dichloro-[(1R,2R)-1,2-cyclohexanediamine-kN,kN′]platine(II) complex (in the following abbreviated as DACHPtCl2) in water with two equivalents of silver nitrate, an elimination of the obtained solid phase and a subsequent reaction of the obtained [(1R,2R)-1,2-cyclohexanediamine-kN,kN′]platinum(II) diaqua-complex dinitrate (in the following abbreviated as platinum(II) diaqua-complex dinitrate) with oxalic acid and/or its alkali metal salts. Analogous (SP-4-2)-diiodo- or dibromo-[(1R,2R)-1,2-cyclohexanediamine-kN,kN′]platine(II) complex can be used instead of DACHPtCl2 in this procedure but DACHPtCl2 is the cheapest. The yield of the obtained oxaliplatin is usually between 60 to 70% and the final yield is usually between 40 to 50% after recrystallization. The platinum(II)diaqua-complex described above can thus be considered as a key synthetic intermediate for oxaliplatin preparation. It has the structural formula II and it is usually in the form of a dinitrate salt but another salts, e.g. sulphate salt, are possible:

The above mentioned general procedure for preparing oxaliplatin has some serious drawbacks.
First drawback is a very long time procedure at room temperature. DACHPtCl2 is a very low soluble in water. The dissolving of DACHPtCl2 particles is very slow and the subsequent reaction with silver salt is very quick which leads to creating platinum(II) diaqua-complex dinitrate and the solid AgCl. Thus, the reaction is running in the thin liquid film on the surface of the particles of DACHPtCl2 as a consequence of this fact and these particles are quickly covered by AgCl layer which blocks further reaction. That is why the reaction of DACHPtCl2 with silver salt usually needs 1 to 3 days at room temperature to reach sufficient conversion according to prior art, e.g. WO 2005/035544 A1; WO 03/004505 A1; EP 1 308 454 A2. It is possible to partially reduce reaction time of DACHPtCl2 with silver salts by increased amount of water and by increased reaction temperature but it is on account of lower yields and increased content of impurities.
Second drawback of the above mentioned general procedure is a high content of silver in prepared oxaliplatin which is usually greater than 100 p.p.m. Any of syntetic impurities, including silver ions, may cause severe adverse effects in the therapeutic use of oxaliplatin. Their presence is to be avoided and so, the prescripted limit for silver content in oxaliplatin is less than 5 p.p.m. Therefore, corresponding purification procedures are the subject of a great wealth of patents and patent applications. Among the most preferred purification processes are those, which use alkaline iodides for the elimination of silver ions and other impurities from the platinum (II) diaqua-complex dinitrate in combination with a large amount of water for the required re-crystallization and washing of the final product. Such a process is described for example in EP 0 617 043 61, WO 03/004505 and EP 0 625 523 B1. For the satisfactory elimination of the Ag+ ions an about threefold excess of iodides is usually recommended. A serious drawback is, however, that iodides parallelly and predominantly react with a surplus of reactive platinum(II) diaqua-complex to the corresponding platinum(II)diiodo complex. These iodo species subsequently react with the spots of Ag+ ions to form insoluble silver iodide precipitates. That is why this chemical purification method requires a considerable time, usually more than 15 hours, to reduce the content of Ag+ ions in the final oxaliplatin below 5 p.p.m. This purification also leads to the contamination and coloration of the product by platinum(II)mono- and diiodo complexes. The crude oxaliplatin must therefore be re-crystallized from water. A further serious drawback results from the re-crystallization of oxaliplatin in water. A large amount of water and a temperature around the boiling point of water are necessary for the re-crystallization of the crude oxaliplatin. Finally, at the boiling point of water side products are easily formed from oxaliplatin even during the short time of the exposure, which represents another serious drawback. The yields of the re-crystallization of the product are less than 70%. If a repeated re-crystallization is necessary, a further loss of the product results. The purified re-crystallized oxaliplatin has still the content of silver ions above 1 p.p.m., usually from 2 to 5 p.p.m.
As follows from the above mentioned prior art, there is a great demand for a process to prepare oxaliplatin in a high purity by an effective method.
The technical problem underlying the present invention is therefore to provide a process for preparing oxaliplatin, which is simple and provides oxaliplatin with a high purity and simultaneously in a high yield.